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SRP058229
Mus musculus
14 Downloadable Samples
Illumina HiSeq 1500
Description
Langerhans cells (LCs) populate the mucosal epithelium, a major entry portal for pathogens, yet their ontogeny remains unclear. In contrast to skin LCs originating from self-renewing radioresistant embryonic precursors, we found that oral mucosal LCs derive from circulating radiosensitive precursors. Mucosal LCs can be segregated into CD103+CD11blow (CD103+LCs) and CD11b+CD103- (CD11b+LCs) subsets. We further demonstrated that similar to non-lymphoid dendritic cells (DCs), CD103+LCs originate from pre-DCs, whereas CD11b+LCs differentiate from both pre-DCs and monocytic precursors. Despite this ontogenetic discrepancy between skin and mucosal LCs, transcriptomic signature and immunological function of oral LCs highly resemble those of skin LCs but not DCs. These findings, along with their epithelial position, morphology and expression of LC-associated phenotype strongly suggest that oral mucosal LCs are genuine LCs. Collectively, in a tissue-dependent manner, murine LCs differentiate from at least three distinct precursors (embryonic, pre-DCs and monocytic) in steady state Overall design: The following cells were isolated from mice (2-4 replicates): Lung DCs, mucosal CD103+ LC, mucosal CD11b+ LC, Skin LC. Transcriptome analysis was performed.
Publication Title
Distinct Murine Mucosal Langerhans Cell Subsets Develop from Pre-dendritic Cells and Monocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
Alas2 gene encodes the rate-limiting enzyme in heme biosynthesis. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis-elements strongly reduced GATA-1-induced Alas2 transcription, heme biosynthesis, and GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing Alas2 function in Alas2 cis-element-mutant (double mutant) cells by providing its catalytic product 5-aminolevulinic acid (5-ALA) rescued heme biosynthesis and the GATA-1-dependent genetic network. We discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. Overall design: G1E-ER-GATA-1 WT and double mutant cells were examined. Untreated WT, beta-estradiol-treated WT, beta-estradiol-treated double-mutant, and beta-estradiol/5-ALA-treated double-mutant cells were subjected to RNA-seq.
Publication Title
Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 258 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Race
View Samples- Homo sapiens
- 194 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
Publication Title
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Race
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recent meta-analyses suggest triple-negative breast cancer (TNBC) is a heterogenous disease. In this study we sought to define these TNBC subtypes and identify subtype-specific markers and targets.
Publication Title
Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Race
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To determine the molecular basis of gene regulation in pancreatic ductal epithelial cells, we developed methods for the isolation of this cell population during mouse development and normal adult homeostasis, as well as in conditions with ductal features (acinar-to-ductal metaplasia (ADM), pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC)). Our technique utilizes the specificity of Dolichos biflorus Agglutinin (DBA) lectin marking the entire normal ductal tree, including terminal intercalated ducts (putative sites of stem or progenitor cells) and ductal structures in ADM and PanIN. We used ferromagnetic-labeled DBA lectin to isolate ductal structures. Ductal cells were isolated under the following conditions: (1) Embryonic Development in wild type mice: E14.5, E15.5, E16.5, and postnatal day 1 (P1); (2) Injury and regeneration (pancreatitis) 0, 1, 3, 5 days following cerulein-induced acute pancreatitis. Cerulein is a cholecystokinin analog which produces a self-limited pancreatitis with injury and subsequent regeneration and repair, completed five days after insult; and (3) Pdx1-Cre;LSL-KrasG12D/+ mice aged 10 and 20 weeks that harbor PanIN lesions and a subset develop PDAC. Ductal/PanIN cells were isolated from these mice and appropriate control mice (Pdx1-Cre;Kras+/+).
Publication Title
The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis.
Sample Metadata Fields
Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer. EXPERIMENTAL DESIGN: 48 patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response. RESULTS: 8 of 40 (20%) patients achieved pCR (95% confidence interval, 9-36%). Of 9 additional patients recruited for protocol-defined toxicity analysis, 8 were evaluable; 42 of 48 (88%) patients had clinical response (16 patients, clinical complete response; 26 patients, clinical partial response). T(1) tumors more frequently exhibited clinical complete response (P = 0.05) and showed a trend to exhibit pCR (P = 0.07). 5 (13%) patients experienced grade 1 cardiac dysfunction during preoperative treatment. Neither HER2 nor estrogen receptor status changed significantly after exposure to trastuzumab and vinorelbine. RNA profiling identified three top-level clusters by unsupervised analysis. Tumors with extremes of response [pCR (n = 3) versus nonresponse (n = 3)] fell into separate groups by hierarchical clustering. No predictive genes were identified in pCR tumors. Nonresponding tumors were more likely to be T(4) stage (P = 0.02) and express basal markers (P < 0.00001), growth factors, and growth factor receptors. Insulin-like growth factor-I receptor membrane expression was associated with a lower response rate (50% vs 97%; P = 0.001). CONCLUSIONS: Preoperative trastuzumab plus vinorelbine is active and well tolerated in patients with HER2-positive, operable, stage II/III breast cancer. HER2-overexpressing tumors with a basal-like phenotype, or with expression of insulin-like growth factor-I receptor and other proteins involved in growth factor pathways, are more likely to be resistant to this regimen.
Publication Title
Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
8 week-old male C57BL6J mice were given Gram-negative endotoxin (LPS O111:B4, 10 mg/kg) intraperitoneally at time 0. 18 hrs thereafter, they were administered 10 ml/kg 0.9% saline. Mice were sacrificed at 0, 18, or 42 hrs after LPS challenge. Kidneys were immediately collected into TRIzol for RNA preparation. Renal function was measured on blood collected at the time of tissue harvest
Publication Title
PGC-1α promotes recovery after acute kidney injury during systemic inflammation in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Danio rerio
- 5 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
drl expression initiates during gastrulation and condenses as a band of cells at the prospective lateral embryo margin. In late epiboly, drl:EGFP is detectable as a band of scattered EGFP-fluorescent cells; after gastrulation, drl:EGFP-positive cells coalesce at the embryo margin that then in somitogenesis break down into the anterior and posterior lateral plate with subsequent cell migrations that form the posterior vascular/hematopoietic stripes and the anterior cardiovascular and myeloid precursors.
Publication Title
Chamber identity programs drive early functional partitioning of the heart.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 11 Downloadable Samples
- Illumina HiSeq 2000, Illumina HiSeq 2500
Description
We report the application of ultrashort metabolic labeling of RNA for high-throughput profiling of RNA processing in Drosophila S2 cells. Overall design: Examination of 3 different labeling timepoints in Drosophila S2 cells.
Publication Title
The kinetics of pre-mRNA splicing in the <i>Drosophila</i> genome and the influence of gene architecture.
Sample Metadata Fields
Cell line, Subject
View Samples